Why are beta blockers (beta-adrenergic blocking agents) used in the management of variceal (esophageal variceal) bleeding?

From the Guidelines

Beta blockers are recommended for patients with variceal bleeding to reduce the risk of rebleeding and improve survival, as evidenced by a recent meta-analysis showing a significant reduction in rebleeding rate and mortality with the use of non-selective beta blockers (NSBBs) 1. The use of beta blockers in the management of variceal bleeding is supported by several studies, including a 2007 study published in Hepatology, which found that non-selective beta blockers, such as propranolol and nadolol, reduce the risk of first variceal bleeding in patients with large- or medium-sized varices by 30% compared to controls 1. The mechanism of action of beta blockers in reducing portal pressure involves two main effects:

• Decreasing cardiac output (beta-1 effect)
• Causing splanchnic vasoconstriction (beta-2 effect) This reduction in portal pressure decreases the risk of variceal rupture and subsequent bleeding. Key points to consider when using beta blockers for variceal bleeding include:
• Starting with a low dose and titrating up as tolerated
• Using non-selective beta blockers, such as propranolol or nadolol, as first-line therapy
• Continuing beta blockers indefinitely unless contraindicated
• Monitoring for side effects, such as fatigue, dizziness, and sexual dysfunction
• Regular follow-up to ensure optimal dosing and adherence A recent study published in 2020 in Clinical and Molecular Hepatology found that the combination of endoscopic variceal ligation (EVL) and NSBBs is the most effective treatment for preventing variceal rebleeding, with a significant reduction in rebleeding rate and mortality compared to EVL alone or NSBBs alone 1. The combination of EVL and NSBBs is recommended as the primary treatment for preventing variceal rebleeding, with the goal of reducing portal pressure and improving survival 1.

From the Research

Mechanism of Action

• Beta blockers work by blocking beta1 receptors, reducing cardiac output, and blocking beta2 receptors, producing splanchnic vasoconstriction and reducing portal flow, consequently reducing portal pressure 2
• The reduction in portal pressure is achieved by decreasing the hepatic venous pressure gradient (HVPG), which is a key factor in preventing variceal bleeding 2

Efficacy in Preventing Variceal Bleeding

• Non-selective beta blockers are effective in preventing first variceal bleeding and re-bleeding in patients with cirrhosis, reducing the bleeding risk from 30 to 15% in primary prophylaxis and from 60 to 42% in secondary prophylaxis in the first year 2
• Beta blockers are also effective in reducing the risk of variceal bleeding in patients with high-risk varices, and are recommended as the treatment of choice for primary prophylaxis 3, 4
• The combination of beta blockers and endoscopic variceal ligation is recommended for secondary prophylaxis, as it has been shown to be more effective than beta blockers alone in reducing the risk of re-bleeding 5

Identification of Responders and Non-Responders

• The only way to know whether a patient has become a responder to beta blocker therapy is to measure the HVPG, which can also identify non-responders who have a higher rate of re-bleeding 2
• Non-responders may require more aggressive therapy, such as adding isosorbide mononitrate to the beta blocker or combining the beta blocker with endoscopic ligation 2

Comparison with Other Therapies

• Beta blockers are equally effective as endoscopic treatment in preventing variceal bleeding, and either modality can be used 3
• The combination of beta blockers and other therapies, such as isosorbide mononitrate, may be more effective than beta blockers alone in reducing the risk of variceal bleeding, but this requires further study 6